Comparative Pharmacodynamic/Pharmacokinetic Studies on Tetracycline Hydrochloride and Its Loaded Nano-emulsion Formula

Abstract

Tetracycline-loaded nanoemulsion (TC-nm) was prepared and characterized using six pseudoternary systems of oils. The stability selected systems was assessed by 3 stages; heat–cool cycles, centrifugation, and finally freeze–thaw cycle. The mean droplet sizes (MDS) of the selected formulae was ranged from 32.33±3.81 to 101.5±9.86 nm. The small size of nanoemulsions was justified by the distribution of the cosurfactant molecules into the surfactant film where 3 S/CoS ratios were 1:1, 1:2 and 2:1. Regarding PDI value of all nanoemulsions range was 0.11± 0.01: 0.41± 0.07. The formulated TC-nm carried ZP values ranged from -25.45±3.43 to -33.47±2.11 mV. TEM showed spherical globules with uniform droplet size.

The HPLC mean plasma tetracycline concentration–time relationship in plasma of 3.5 kg white male New Zealand rabbits following oral or I.V a single dose of 50 mg/kg b.wt of either tetracycline hydrochloride (TC-hcl) or TC-nm . Following a single I.V injection plasma concentration exceeded 0.026 ± 0.0055 and0.023 ± 0.0040 µ/mL for at least 12 hours inTc- hcl and TC-nm, respectively. The pharmacokinetic variables in I.V had higher distribution volume V2 (0.304 ± 0.062 L/kg) in TC-nm than for TC- hcl (0.261 ± 0.1252L/kg) and was slowly cleared from the central compartment (0.379 ± 0.0741 L.h/kg) in TC- hcl than TC-nm (0.27 ± 0.0928 L.h/kg) after I.V injection. The pharmacokinetic variables of a single oral dose indicated that TC-hcl was rapidly absorbed and eliminated with significant longer absorption half-life t1/2ka 0.518 ± 0.0908h and elimination half life time t0.5Beta 4.215 ± 1.6613 h for TC-nm than for TC- hcl (t0.5ka 0.518 ± 0.0908h, t.0.5Beta 3.331 ± 0.6756h.) with calculated Cmax of (6.380 ± 0.9142 μg/ml and 6.781 ± 0.6664 μg/ml) achieved at prolonged calculated tmax (0.869 ± 0.0599 and 0.397 ± 0.0330 h.) in TC-nm than in TC-hcl treated rabbits, respectively. A Significant